Required features of a biomolecule delivery system are to maintain the biomolecule structural integrity during encapsulation, storage and release, and to have a mechanism for enabling suitable release kinetics.
One common application is that of protein drug delivery. The present technology in protein drug delivery applications is largely polymer-based. There are several disadvantages with polymer-based systems as encapsulants for biological entities such as proteins:                Polymer production can involve use of chemicals and/or elevated temperatures, which can denature proteins;        Typically the release mechanism of protein from a polymer matrix is erosion (i.e. dissolution) of polymer matrix. Erosion (and thus release) rates are usually dependent on the chemical environment of the polymer particle (e.g. pH dependent). Erosion can also give rise to degradation by-products which will denature the proteins;        Polymer typically have hydrophobic surfaces, which require surface treatment to introduce hydrophilicity and thus enhanced stability in the blood;        Proteins may be damaged/denatured on storage due to for example dehydration;        Polymeric gels can undergo severe shrinkage during drying which can result in squeezing of the encapsulated protein and resulting in a change in their conformation.        
WO 01/62232 (Barbé and Bartlett) refers to the incorporation of biological active materials into ceramic encapsulants, however, the chemistry described in the patent is not ideal for encapsulation and release of larger biomolecules. The short-chain alcohols released on hydrolysis of the silicon alkoxide precursors used to form the silica spheres are known to denature protein molecules, leading to significant loss of biological activity. In addition, the sol-gel reactions are usually conducted in presence of an acid or base catalyst, resulting in pHs incompatible with most biological molecules. Also, proteins range in size up to about 3000 kDa, and may exceed 10 nm diameter. The micropores formed in acidic conditions are commonly too small to allow release of molecules of this size, although the mesopores formed under basic conditions are larger and may enable release of small proteins. Ideally a system is required in which the pH can be maintained within the typical physiological range of ˜5-8, conditions which are not suitable for catalysing the hydrolysis of silicon alkoxides.
JP5 261274 (Lion Corp.) describes a process for encapsulating biomolecules in a ceramic matrix. However the particles made by the patented process are not designed for controlled release of the biomolecules. In addition, the process exposes the biomolecules to harsh conditions such as extremes of pH and high shear which may denature or otherwise harm sensitive biomolecules, in particular proteins. Further, the rapid flocculation used in the process is likely to lead to very broad and uncontrolled particle size distributions.
There is therefore a need for a delivery system for biological entities which displays desirable release kinetics and is capable of maintaining the structural integrity of the biological entity during encapsulation, storage and release.